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Introduction
Gastric cancer, malignancy
GASTRIC CANCER
Gastric cancer (GC) is the fifth most common malignancy worldwide. The highest incidence of GC exists in East Asian countries, especially in China and JapanIn the second-line therapy setting, ramucirumab was the only molecular-targeted drug in a global phase III clinical trialThymidylate synthase is a well-established ...
PMC10546090
Materials and methods
PMC10546090
Patient screening and stratification
ONCOLOGY, RECURRENT DISEASE, ADENOCARCINOMA, METASTATIC DISEASE
The patient inclusion criteria were as follows: age ≤ 18 years; histologically-proven gastric or esophagogastric junction adenocarcinoma; measurable and/or assessable metastatic disease according to RECIST 1.0 criteria, or locally recurrent disease associated with one or more measurable lymph nodes; Eastern Cooperative...
PMC10546090
Treatment
histologically-proven
This was a randomized, multicenter, open-label, phase II clinical study in patients with histologically-proven, inoperable, locally advanced or MGC. Patients were randomly assigned (1:1) to receive raltitrexed (3 mg/m
PMC10546090
Evaluation and outcomes
tumor, death, Toxicities, Tumor, Tumors, PD, Toxicity, Cancer
DISEASE PROGRESSION, TUMOR, TUMOR, DISEASE, TUMORS, CANCER
A complete medical history was obtained and a physical examination was performed before randomization, including a complete blood count (CBC), blood chemistries, and tumor assessments. Tumor measurements were obtained every 6 weeks until progression was demonstrated in both arms, as assessed by Response Evaluation Crit...
PMC10546090
Statistical analysis
SECONDARY
The primary endpoint (PFS) and secondary endpoints (OS, ORR, and safety) were determined and analyzed. The Kaplan-Meier statistical method was used to calculate the PFS and OS. ORRs were compared using a χ
PMC10546090
Results
PMC10546090
Patients
cancer, RP
CANCER
A total of 148 patients [raltitrexed plus paclitaxel (RP) group, Patient and cancer baseline characteristics RP, raltitrexed plus paclitaxel; P, paclitaxel.
PMC10546090
Treatment
thrombocytopenia, PD, Neutropenia, neutropenia
NEUTROPENIA, ADVERSE EVENTS, THROMBOCYTOPENIA, ADVERSE EVENT, NEUTROPENIA
The median duration of therapy was 3.5 cycles for RP (range, 1-15 cycles) and 4 cycles for P (range, 1-12 cycles). Dose reductions occurred in 12 patients in the RP group (16.4%) and 8 patients in the P group (10.7%). Neutropenia and thrombocytopenia were the most prominent adverse events leading to cycle delay and dos...
PMC10546090
Efficacy: primary end points (OS and PFS)
tumor, gastric cancer
TUMOR, GASTRIC CANCER
At a median follow-up duration of 13 months, the median OS was longer in the intention-to-treat (ITT) population of the RP group than the P group (10.2 months, 95% CI = 8.2-12.2 ITT, Kaplan-Meier estimates of time to overall survival among advanced gastric cancer patients treated with RP or P.ITT, Kaplan-Meier estimate...
PMC10546090
Efficacy: secondary end point (ORR)
BEST
The ORR was equal for the RP (6.8%) and XELOX groups (4.0%) (Best overall response rateRP, raltitrexed plus paclitaxel; P, paclitaxel.
PMC10546090
Safety and Quality of life (QOL): secondary end point
toxicities, neutropenia
ADVERSE EVENTS, NEUTROPENIA
Grade 3-4 treatment-related adverse events occurred in 60.6% and 57.5% of patients in the RP and P groups, respectively. Frequent grade 3-4 toxicities in the RP and P groups were neutropenia (11% Major treatment-based adverse eventsRP, raltitrexed plus paclitaxel; P, paclitaxel.
PMC10546090
Discussion
toxicity, hepatotoxicity
This study was initiated in 2014. Second-line standard treatment is still single-agent chemotherapy and 3In the present study the combination dose of P was adjusted to 240 mg/mAs expected, the ORR was low in each group, but the DCR was 56.2% and 36% in the combination and P only groups, respectively. Although the OS an...
PMC10546090
Conclusions
It is our opinion that appropriate dosage and usage of P and antimetabolites may have a greater role in 2
PMC10546090
Conflict of interest statement
No potential conflicts of interest are disclosed.
PMC10546090
Author contributions
Conceived and designed the analysis: Zhiyu Chen, Wen Zhang, Xiaodong Zhu, Lei Yang, and Weijian Guo.Collected the data: Xiaowei Zhang, Lixin Qiu, and Mingzhu Huang.Contributed data or analysis tools: Xiaoying Zhao, Chenchen Wang, and Wenhua Li.Performed the analysis: Weijian Guo.Wrote the paper: Xiaoying Zhao.
PMC10546090
Data availability statement
The authors confirm that the data supporting the findings of this study are available within the article.
PMC10546090
References
PMC10546090
Abstract
Daprodustat, Oral daprodustat, chronic kidney disease, anemia
ANEMIA
Daprodustat is an oral small molecule hypoxia‐inducible factor (HIF) prolyl hydroxylase inhibitor (PHI) approved in Japan and the United States for the treatment of anemia associated with chronic kidney disease. This phase 1, nonrandomized, 2‐period, crossover study in 6 healthy men characterized and quantified the met...
PMC10603292
Abbreviations
kidney diseasedisintegrations
absorption, distribution, metabolism, and excretionaccelerator mass spectrometryarea under the curvechronic kidney diseasedisintegrations per minutedrug‐related materialerythropoietinhypoxia‐inducible factorhigh‐performance liquid chromatographyHPLC‐tandem mass spectrometryliquid chromatography–tandem mass spectrometry...
PMC10603292
INTRODUCTION
Anemia, CKD, chronic kidney disease, anemia
ANEMIA, ANEMIA
Anemia is common in patients with chronic kidney disease (CKD). Mechanisms contributing to anemia in these patients include deficiency of Following single oral dosing of [
PMC10603292
METHODS AND MATERIALS
PMC10603292
Subjects and study design
The design and clinical pharmacokinetics of daprodustat in the crossover mass balance study in 6 healthy male participants have been previously described.
PMC10603292
Chemicals and reagents
[Structures of the reference standards are shown in Figure Chemical Structures of Daprodustat and Metabolites. Structures represent the predominant single stereoisomeric form of human circulating metabolites M2, M3, M4, M5, M6, and M13.
PMC10603292
Collection of samples
upper gastrointestinal fluid
Duodenal bile samples were collected for metabolite characterization on Entero‐Test bile strings, a commercially available noninvasive procedure to collect upper gastrointestinal fluid.
PMC10603292
Sample pooling and pretreatment
PMC10603292
Plasma
dryness
Two pooled plasma samples from TP2 were prepared from the six human subjects based on total radioactivity in the samples. A primary pool comprising approximately 95% of the total plasma radioactivity was created according to the area under the response‐time curve (AUC) concentration‐time proportional pooling method.The...
PMC10603292
Urine
Urine samples from TP2 were analyzed without pooling since >95% of cumulative urinary dose excretion occurred during the first 24 h.
PMC10603292
Feces
Weighed aliquots of selected fecal homogenates from TP2 were pooled in proportion to total sample weight for each human subject to include the majority of excreted radioactivity. The time range of the pooled fecal homogenates varied from 24 to 120 h postdose, among subjects, depending on the rate of radioactivity excre...
PMC10603292
Duodenal bile
AMS
COLD
To assess the drug‐related material (DRM) arising from the radiolabeled intravenous dose (TP1), individual bile strings were extracted with either acetonitrile or water in two separate extraction procedures. An aliquot of 500 μL from each acetonitrile or water extract was pipetted into a scintillation vial and mixed wi...
PMC10603292
Quantitative radio‐HPLC analysis
dryness
Radio‐HPLC analysis was conducted on selected urine, fecal, and plasma samples on a 1200 HPLC system (Agilent Technologies, Palo Alto, CA). Radio‐HPLC conditions are described in Data Urine and feces samples were injected onto the HPLC and the column eluate from each sample was fractionated into a set of four LumaPlate...
PMC10603292
HPLC‐UV+AMS analysis for bile samples
two‐step
The pooled bile string extract solution was spiked with nonradiolabeled standards, mixed and injected (100 μL), then chromatographed by HPLC. The HPLC column eluate was fractionated (12‐s intervals between 15 and 55 min) and collected into prebaked small quartz tubes containing copper oxide wire.Additionally, replicate...
PMC10603292
Mass spectrometric analysis
LC‐MS
PMC10603292
Nomenclature of targets and ligands
Key protein targets and ligands in this article are hyperlinked to corresponding entries in
PMC10603292
RESULTS
PMC10603292
HPLC column recovery
duodenal bile extracts
SEPARATION
HPLC column recoveries of selected urine (TP2), selected feces (TP2), and duodenal bile extracts (TP1) were essentially complete, indicating no or minimum loss of radioactivity during chromatographic separation (Table The retention times and fragment of all metabolites in human plasma, urine and bile samples.MSMSMSMSMS...
PMC10603292
Radio‐HPLC profiles
PMC10603292
Plasma (TP2)
The levels of total radioactivity in the 0–8 h and 10–12 h plasma pools were 1492 DPM/g and 121 DPM/g, respectively, corresponding to 268 ng daprodustat equivalents/g and 22 ng daprodustat equivalents/g. Overall recovery of radioactivity following sample preparation was 85 and 69% for the 0–8 h and 10–12 h pools, respe...
PMC10603292
Urine (TP2)
MINOR
Recovery of urine radioactivity following centrifugation was complete, indicating no loss of drug‐related components during sample processing. The 0–24 h urine samples that were analyzed represented 97% of total cumulative radioactivity excreted in the urine. Minor qualitative differences in the urine radio profiles we...
PMC10603292
Feces (TP2)
MINOR
The analysis of pooled fecal homogenates showed that 99% of the total cumulative radioactivity in the excreta was recovered, indicating little loss of drug‐related components during sample preparation. As with urine, minor qualitative differences in the radio profiles of fecal extracts were observed across subjects. Fi...
PMC10603292
Duodenal bile (TP1)
Unchanged daprodustat, duodenal bile extract
MINOR
Figure Reconstructed HPLC‐AMS radiochromatogram and UV‐chromatogram of pooled and diluted duodenal bile extract following a single intravenous Infusion of [Unchanged daprodustat accounted for only 0.5% of biliary radioactivity, indicating extensive hepatic metabolism of the parent compound. The metabolic profile in bil...
PMC10603292
DISCUSSION
duodenal bile, duodenal bile sampling, CKD, anemia
ANEMIA
Following a single oral dose of [Consistently, previous steady‐state clinical data in patients with anemia associated with various stages of CKD also indicated that daprodustat was the principal circulating DRM in human plasma, measured at up to 55% by AUC ratio.Comprehensive safety evaluations of the three major metab...
PMC10603292
AUTHOR CONTRIBUTIONS
Liangfu Chen and Guoying Tai contributed to the concept and design, performed data analysis, and helped to write the draft. Fangming Xia conducted experiments, contributed new reagents or analytic tools, and performed data analysis. Cathy Chen contributed to the concept and design, conducted experiments, contributed ne...
PMC10603292
CONFLICT OF INTEREST STATEMENT
Liangfu Chen, Cathy Chen, Adrian Pereira, Xiusheng Miao, Graeme Young, and Guoying Tai are employees of and hold stock in GSK. Fangming Xia, Claire Beaumont and Jill Pirhalla are former employees of GSK.
PMC10603292
ETHICS STATEMENT
The clincial study was approved by an independent ethics committee and was conducted according to the recommendations of Good Clincial Practice and the Declaration of Helsinki. All subjects provided written informed consent to participate in the study.
PMC10603292
Supporting information
Data S1. Click here for additional data file.
PMC10603292
ACKNOWLEDGMENTS
Funding for this study was provided by GSK. All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. Funding for this study was provided by GSK. Editorial support, Meher Dustoor, PhD and Sarah Hummasti, PhD (assembling tables and figures, collating author...
PMC10603292
DATA AVAILABILITY STATEMENT
Anonymized individual participant data and study documents can be requested for further research from
PMC10603292
REFERENCES
PMC10603292
Supplementary Information
death, ST-segment elevation myocardial infarction, cardiac death, contrast-associated acute kidney injury
CONTRAST-ASSOCIATED ACUTE KIDNEY INJURY, CARDIAC DEATH, SECONDARY, REGRESSION, EVENTS
To assess the efficacy of modified hydration on contrast-associated acute kidney injury (CA-AKI) in ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (pPCI). A total of 438 patients were randomly assigned to 2 groups. The traditional hydration group (group I) was given ...
PMC9883347
Keywords
PMC9883347
Introduction
contrast-induced acute kidney injury, ST-segment elevation myocardial infarction, CI-AKI, contrast-associated acute kidney injury
CONTRAST-INDUCED ACUTE KIDNEY INJURY, CONTRAST-ASSOCIATED ACUTE KIDNEY INJURY
The widespread adoption of primary percutaneous coronary intervention (pPCI) has significantly improved the cardiovascular outcomes of ST-segment elevation myocardial infarction (STEMI), however, the incidence of contrast-associated acute kidney injury (CA-AKI), which has replaced the definition of contrast-induced acu...
PMC9883347
Methods
PMC9883347
Study population
MALIGNANT TUMOR, CONGESTIVE HEART FAILURE, ACUTE RESPIRATORY FAILURE
A total of 508 STEMI patients undergoing pPCI at the Cardiovascular Center of Beijing Friendship Hospital from November 2018 to October 2021 were enrolled in this study. 70 patients were excluded according to the exclusion criteria including acute respiratory failure; continuous renal replacement therapy or prior kidne...
PMC9883347
Study protocol
Eligible patients were randomly assigned to group I (traditional hydration group) and group II (modified hydration group). The traditional hydration group received a continuous intravenous infusion of isotonic saline at a rate of 1 ml/kg/h for 24 h at the beginning of pPCI [
PMC9883347
Other data collection and definitions
chest pain, myocardial injury
LEFT BRANCH BUNDLE BLOCK, RENAL DISEASE, LEFT VENTRICULAR HYPERTROPHY
Venous blood samples were taken from all patients pre-pPCI and then 24, 48 and 72 h after pPCI, samples were used for measurement of serum creatinine and estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) equation in (ml/min/1.73mSTEMI was diagnosed based on the diagnostic...
PMC9883347
Coronary angiography and PCI
stenosis, STEMI
STENOSIS
Patients with STEMI received coronary angiography immediately after admission to the catheter laboratory, with a digital subtraction machine. The coronary angiography was performed by cardiologists in Beijing Friendship Hospital, and all STEMI patients received PCI surgery as soon as possible after admission to open th...
PMC9883347
Study endpoints
death, cardiac death, chest pain, myocardial necrosis, angina pectoris, AKI, non-cardiac death, Cardiac death
MYOCARDIAL INFARCTION (MI), SUDDEN DEATH, CARDIAC EVENTS, CARDIAC DEATH, MYOCARDIAL NECROSIS, SECONDARY, SAID, EVENTS, HEART FAILURE, CARDIAC DEATH
The primary endpoint of the study was the incidence of CA-AKI, which identifies events based on Improving Global Outcomes (KDIGO) serum creatinine criteria [increase in serum creatinine by ≥ 26.5 µmol/l (0.3 mg/dl) or increase in serum creatinine by ≥ 1.5 times baseline value]. AKI was said to be present if these chang...
PMC9883347
Statistical analysis
SD
REGRESSION, SECONDARY
Depending on the distribution of the data, continuous variables were expressed as mean value ± SD or median and interquartile range (IQR). Frequencies and percentages were used to describe categorical data. Differences between continuous and categorical variables were assessed using Student’s T-test, analysis of varian...
PMC9883347
Results
PMC9883347
Kaplan–Meier analysis of secondary endpoint
death, cardiac death
SECONDARY, CARDIAC DEATH
During a median follow-up period of 22.4 months, the incidence of MACEs was 21.1% in the CA-AKI group and 9.3% in the no CA-AKI group. The incidences of all-cause death and cardiac death were 10.5% and 7.9% in the CA-AKI group, 0.5% and 0.5% respectively in the no CA-AKI group (all Kaplan–Meier curve for secondary endp...
PMC9883347
Discussion
death, cardiac death, myocardial ischemia, STEMI
CARDIAC DEATH, MYOCARDIAL ISCHEMIA
In this study cohort with STEMI patients undergoing pPCI, we found that the patients with lower creatinine were more likely to occur CA-AKI. The incidence of CA-AKI and creatinine levels at different time points were not significantly different between the traditional hydration group and the modified hydration group. C...
PMC9883347
Study limitations
pre-PCI, renal insufficiency
RENAL INSUFFICIENCY
Despite the precise randomization, which results in an unimportance difference in baseline characteristics of the two groups, our study has several limitations. First, although our study had a relatively large sample size, the single-center study was also a limitation. Second, although many potential interfering covari...
PMC9883347
Conclusion
According to the findings, although this difference was not statistically significant, the modified hydration also relatively reduced the incidence of CA-AKI after pPCI. CA-AKI may be related to lower creatinine, WBC count and NT-proBNP. The relationship between CA-AKI and mortality strengthened as creatinine times abo...
PMC9883347
Supplementary Information
Below is the link to the electronic supplementary material.Supplementary file1 (DOCX 168 KB)
PMC9883347
Acknowledgements
The authors gratefully acknowledge the contributions of all staffs who work on the Cardiovascular Center of Beijing Friendship Hospital Data Bank (CBD BANK).
PMC9883347
Author contributions
HC and HWL: contributed to the conception or design of the work. LL and LZ: contributed to the acquisition, analysis, or interpretation of data for the work. HC and WPL: contributed discussion and edited manuscript. LL: drafted the manuscript. All authors critically revised the manuscript. All authors gave final approv...
PMC9883347
Funding
This study was supported by National Key R&D Program of China (2021ZD0111004), Natural Science Foundation of China (No. 82070357), Beijing Municipal Administration of Hospital Incubating Program (No. PX2018002), Beijing Key Clinical Subject Program, and GE Healthcare 【GE Healthcare (Shanghai) Co. Ltd 】.
PMC9883347
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC9883347
Declarations
PMC9883347
Conflict of interest
The authors declare that they have no competing interests.
PMC9883347
Ethical approval and consent to participate
The study data collections were approved by the Institutional Review Board of Beijing Friendship Hospital, Capital Medical University, and written informed consent was obtained from all patients.
PMC9883347
Consent for publication
Not applicable.
PMC9883347
References
PMC9883347
Background
cancer
CANCER
Edited by: Yao Song, Hong Kong Polytechnic University, Hong Kong SAR, ChinaReviewed by: Jing Luo, Shenzhen University, China; Mohammed Amir Rais, University of Algiers, Algeria; Jane G. Payumo, Michigan State University, United States; Kittisak Jermsittiparsert, University of City Island, Cyprus; Jeff Bolles, Universit...
PMC10310936
Objective
breast cancer
BREAST CANCER
The objective of our study is to access the factors influencing breast cancer health education through short videos on efficiency and quality.
PMC10310936
Methods
Three pairs of videos about breast health were created and participants completed questionnaires before and after watching the videos. A paired
PMC10310936
Results
Watching short videos can significantly increase viewers’ knowledge of related health topics (
PMC10310936
Conclusion
cancer
CANCER
A uniformed interpreter, BGM and a progress bar are factors influencing the efficiency of short health videos. They can be applied in video making to explore better ways of promoting cancer health education in the new mobile Internet environment.
PMC10310936
1. Introduction
visual and auditory factors, breast cancer, cancer, lung cancer, Cancer
BREAST CANCER, CANCER, BREAST CANCER, LUNG CANCER, CANCER
In the past decade, the importance of social media as a means of disseminating health information has grown (Breast cancer is the most prevalent cancer among women and a worldwide public health problem. Global Cancer Statistics 2020 pointed out that breast cancer has surpassed lung cancer as the cancer with the highest...
PMC10310936
2. Methods
PMC10310936
2.2. Materials and methods
We used a pretest-posttest control group design, which we developed on the basis of literature on the effect of online short videos. This study was conducted to assess the influence of three variables on the quality of breast health public education (Study design.
PMC10310936
2.3. Video preparation
Familial aggregation of, hyperplasia of mammary glands, breast cancer
BREAST CANCER
To present the influence of the three variables mentioned above, the video production team, consisting of proficient short video producers and science popularization workers with medical backgrounds, created three groups of videos on three topics: (1) hyperplasia of mammary glands (2) Familial aggregation of breast can...
PMC10310936
2.4. Questionnaire
To measure the effectiveness of the three variables mentioned above, we developed 2 questionnaires for the participants to complete before and after watching the three pairs of videos (The questionnaires passed the verification of Credamo, which evaluated their negative effect. Eligible Credamo users could access the s...
PMC10310936
2.5. Sample size
For each of the videos, participants were recruited through the Credamo platform to watch the video and fill out the questionnaires. The survey lasted from April 24 to April 29, 2022, and involved 780 participants from 31 provincial-level administrative regions (excluding Hong Kong, Macao, and Taiwan). Of the 780 respo...
PMC10310936
2.6. Statistical analysis
Descriptive statistics were calculated for the participants’ demographic data. A paired
PMC10310936
3. Results
PMC10310936
3.1. Public attitude toward health educational videos
A 5-point scale was used to evaluate the public attitude toward the videos. A score of 3 points indicated a neutral attitude. The average score was calculated and is displayed in Public attitude toward health education videos.*Indicates significance at the
PMC10310936
3.2. The effect of videos on promoting public breast health literacy
breast diseases
BREAST DISEASES
To assess the effectiveness of the videos, the paired Generally, the pretest scores were lower than the posttest scores in each group and there was a significant difference between the pretest and posttest scores in each group (Cognition and attitude to breast diseases of participants.*Indicates significance at the Spe...
PMC10310936
3.3. Video creation influencing factors on the health education effect
These experiments, which were designed to verify the influence of clothing, the progress bar, and BGM on the video science popularization effect, all adopted a mixed design, and each experiment included an intrasubject variable and an intersubject variable. Among them, the test time (pretest/posttest) was the intrasubj...
PMC10310936
4. Discussion
PMC10310936
4.1. Factors influencing health video effects
Previous studies of influencing factors of health video creation have focused on three main aspects: (1) conception of the script [choices of different framing techniques, choices of specific examples and general conceptions, combinations of multiple theories to convey educational messages, etc. (The effect of BGM on l...
PMC10310936
4.2. Current health video-creation situation and advice for professional health video creators
According to the 49th Statistical Report on China’s Internet Development released by CNNIC in December 2021, the utilization rate of short videos among Chinese netizens was 90.5%, reaching 934 million (However, the spread of short videos about health science popularization is currently not a positive situation. The eme...
PMC10310936
4.3. Limitations
This study has some limitations. First, we directly recruited the video subjects and played relevant videos for them. This test method is insufficient for simulating the situation in which the subjects browse the video on the short video platform. Second, the number of participants was limited, meaning that subgroup an...
PMC10310936
5. Conclusion
visual and auditory factors
BREAST CANCER
This study researched the impact of visual and auditory factors on the transmission effect of medical science short videos designed for science popularization in breast cancer. In the form of a questionnaire, we investigated the effect difference of participants before and after watching the videos to verify users’ inf...
PMC10310936
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
PMC10310936
Ethics statement
The studies involving human participants were reviewed and approved by Ethics Committee of Shantou University Medical College. The patients/participants provided their written informed consent to participate in this study.
PMC10310936
Author contributions
X-YX and H-YL: conceptualization. W-JZ, X-TH, and Y-YM: methodology. DZ: formal analysis. Y-KL: investigation. LX: data curation. Q-RX, P-ZW, and J-ZD: writing—original draft preparation and project administration. X-YX, LX, and H-YL: writing—review and editing. DZ and Y-KL: supervision. Y-KL, X-YX, and H-YL: funding a...
PMC10310936
Funding
This work was supported by grants from the Youth Innovative Talents Project of Education Department of Guangdong Province (2019WQNCX028), Philosophy and Social Science Planning Project of Guangdong Province in China (GD21YXW01), Research Start-up Funding Project of Shantou University (STF19026), the National Undergradu...
PMC10310936
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
PMC10310936