Explore the vast range of titles available.

ObjectiveTo describe temporal trends in initiation, dose intensity, utilisation and potentially inappropriate prescribing of proton pump inhibitors (PPIs) among recent initiators in an urban Chinese outpatient setting.DesignRetrospective, annual identification of recent PPI initiators using a 1-year washout definition (repeated cross-sectional approach).SettingOutpatient prescriptions recorded in the hospital information system of Jinshan Hospital Affiliated to Fudan University, Shanghai, China, 2013–2021.ParticipantsAdults aged ≥18 years who initiated PPI and had no PPI prescription in the preceding year.Outcome measuresPrimary and secondary outcome measures annual initiation rates (overall and stratified by sex, age group, dose intensity and indication), utilisation metrics (defined daily dose/1000 inhabitants/day, defined daily cost, drug utilisation index) and components of potentially inappropriate prescribing (indication-related, prophylaxis-related and incomplete diagnosis).ResultsAmong 114 241 recent initiators (mean age 48.47 years; 51.43% female), initiation rates increased from 1.79% (95% CI 1.76% to 1.83%) in 2013 to 2.79% (2.74% to 2.83%) in 2021 (p<0.001), with the steepest rise in adults aged 18–34 years. High-dose initiation peaked in 2019 and then declined, while standard-dose initiation increased after 2019. Across 2013–2021, potentially inappropriate indication-related prescribing decreased (30.94% in 2013 to 10.36% in 2021), whereas prophylaxis-related prescribing remained common.ConclusionsPPI initiation increased substantially over the past decade, particularly among younger adults. These patterns raise concerns about potential overuse and suboptimal prescribing. The results underscore the need for targeted prescription review and deprescribing-oriented stewardship, with particular attention to young adults, prophylactic indications and dose optimisation.

ObjectivesThis study aimed to characterise the prescribing patterns and evaluate the appropriateness of the prescribed proton pump inhibitors (PPIs) in adult patients via a review of electronic medical records in a single-centred hospital.DesignAll patients admitted to the outpatient department of Jinshan Hospital, Fudan University, Shanghai, between 1 January 2018 and 31 December 2018 were evaluated. Individuals aged 18 years or above and with at least one dispensing for PPIs were identified as PPI users. New PPI users were defined as a subject who did not receive any dispensing for PPIs in the year prior to the index date. Baseline characteristics of PPI users and their therapies were described by treatment indication, economic indicators and co-prescription, overall and separately.SettingThe prescription database was retrieved from the hospital information system of Jinshan Hospital, Fudan University.ResultsAmong 18 435 identified PPI users in 2018, 14 219 patients (aged 18 years or above) who had at least one dispensing PPIs were new users (77%), and among them, men accounted for 47%. The mean treatment duration was 23 days. Omeprazole was the most commonly prescribed drug. PPIs are inappropriately prescribed in 50% (13 589/25 850) of prescriptions. Prescription appropriateness analysis indicated that the unapproved indications for PPI new users accounted for 47%; among them, the proportion of gastritis diagnosis was 34%. The proportion of PPI new users with co-prescription of glucocorticosteroids (GCs) who have risk factors accounted for 24% and lower than other co-prescription. A majority of PPI users (73%) reported high-dose PPI prescription. The defined daily dose of oral pantoprazole was the highest, and injectable omeprazole had the highest defined daily cost. In contrast, only the drug utilisation index value of oral esomeprazole was less than 1.0.ConclusionThe results indicate the challenge of PPI use was accompanied by unapproved indications, frequent inappropriate co-prescription with GCs and excessive dosages. Efforts should be paid to promote rational use and ensure the choice of suitable PPI therapy in the future.

Background Icaritin, an active ingredient of the Chinese herb Epimedium, plays an anti-tumor role in liver cancer by inhibiting the proliferation of hepatocellular cells and promoting their apoptosis. In China, phase II and a large phase III clinical trial of icaritin reagent for the treatment of hepatocellular cancer is under-going, but the specific mechanism of icaritin action was unclear. Alpha-fetoprotein (AFP), an oncofetal protein, produced in the healthy fetal liver and yolk sac. Intracellular AFP promoted cellular proliferation and inhibited cellular apoptosis in hepatocellular carcinoma (HCC). The study was aimed to investigate the effect of icaritin on HCC through p53/AFP pathway. Methods Real-time RT PCR and western blot were used to detect p53 and AFP expression levels in HCC cells treated with icaritin. The mechanism of icaritin affecting p53 expression was verified by ubiquitination experiment, and the binding activity of icaritin on p53 in AFP promoter region was verified by luciferase experiment. EdU, MTT and flow cytometry were used to determine whether icaritin affected HCC cellular proliferation and apoptosis through p53/ AFP pathway. Expression levels of p53 and AFP in xenograft mouse model were determined by western blotting. Results Our results showed icaritin inhibited AFP expression at mRNA and protein level. AFP was also identified as the target gene of the p53 transcription factor. Icaritin abrogated murine double minute (Mdm) 2-mediated p53 ubiquitination degradation to improve the stability of p53. Up-regulated p53 protein levels then transcriptionally inhibited the AFP promoter. Icaritin-mediated decrease of AFP through Mdm2/p53 pathways inhibited HCC cellular proliferation and promoted HCC cellular apoptosis. Conclusion Our findings revealed the mechanism of icaritin in promoting apoptosis and inhibiting proliferation in liver cancer cells. The regulatory mechanism of icaritin in AFP protein down-regulation provides a theoretical and experimental basis for further research into new drugs for the treatment of liver cancer.

Introduction: Adverse drug reactions (ADRs) represent a public health problem worldwide that deserves attention due to the impact on mortality, morbidity, and healthcare costs. Drug–drug interactions (DDIs) are an important contributor to ADRs. Most of the studies focused only on potential DDIs (pDDIs), while the detailed data are limited regarding the ADRs associated with actual DDIs. Methods: This retrospective study evaluated ADRs reported between 2011 and 2020 in a tertiary hospital. The causality and severity of ADRs were evaluated through the Naranjo Algorithm and Hartwig’s scale, respectively. Preventability classification was based on the modified Schoumock and Thornton scale. For ADRs with at least two suspected drugs, pDDIs were identified according to the Lexi-Interact. We further checked whether the ADR description in the reports corresponded to the clinical consequences of the pDDIs. Results: A total of 1,803 ADRs were reported, of which 36.77% ADRs were classified as mild, 43.26% as moderate, and 19.97% as severe. The assessment of causality showed that the distributions of definite, probable, and possible categories were 0.33%, 58.68%, and 40.99%, respectively. A total of 53.97% of ADRs were identified as preventable ADRs, while 46.03% were recognized as unpreventable. The severity of ADRs was significantly correlated with age, the number of suspected drugs and preventability. Antimicrobial agents were the most common implicated pharmacological group, and the most frequently affected system was the gastrointestinal system. Considering individual drugs, aspirin was the most frequently reported drug. Among 573 ADRs with at least two suspected drugs, 105 ADRs were caused by actual DDIs, of which only 59 and 6 ADRs were caused by actual DDIs in category D and X, respectively. The most frequent drugs involved in actual DDIs of category D were aspirin and heparin, with the majority of ADRs being gastrointestinal bleeding. Conclusion: This study analyzed the pattern of ADRs in detail and obtained clinical evidence about ADRs associated with actual DDIs. These findings may be useful to compare patterns between different centers and to design preventive strategies for ADRs. Continuous education and training should be provided for physicians regarding the knowledge and recognition of ADRs associated with DDIs.

Rac GTPase activating protein 1 (RacGAP1) can regulate cytokinesis and cell differentiation. The oncogenic role of RacGAP1 has been partially studied in gastric cancer, colorectal cancer, and breast cancer. In the present study, we endeavor to evaluate its expression and functions in epithelial ovarian cancer (EOC). We retrospectively collected the clinicopathological information of 117 patients who underwent curative surgery for EOC. Expression of RacGAP1 protein in primary tumor tissues was evaluated by immunohistochemistry, which was significantly associated with tumor pathological grade, tumor stage, and lymph node metastasis. Patients with lower RacGAP1 level had a longer survival time and lower recurrence risk. Multivariate results identified the independent prognostic role of RacGAP1 for both recurrence and survival in EOC patients. Cellular studies showed that RacGAP1 can positively regulate the activation of RhoA and Erk proteins. In addition, wound healing assay and Transwell assay found that RacGAP1 can up‐regulate the migration and invasion process of EOC cells, respectively. In all, our results not only confirmed the prognostic role of RacGAP1 for recurrence and survival in EOC patients, but also highlighted its possible potency for drug development. Epithelial ovarian cancer (EOC) patients with lower Rac GTPase activating protein 1 (RacGAP1) level had a longer survival time and lower recurrence risk. RacGAP1 can positively regulate the activation of RhoA and Erk proteins, thus up‐enhance the migration and invasion process of EOC cells.

Human observers can extract the mean emotion from multiple faces rapidly and precisely. However, whether attention is required in the ensemble coding of facial expressions remains debated. In this study, we examined the effect of attentional load on mean emotion processing with the dual-task paradigm. Individual emotion processing was also investigated as the control task. In the experiment, the letter string and a set of four happy or angry faces of various emotional intensities were shown. Participants had to complete the string task first, judging either the string color (low attention load) or the presence of the target letter (high attention load). Then a cue appeared indicating whether the secondary task was to evaluate the mean emotion of the faces or the emotion of the cued single face, and participants made their judgments on the visual analog scale. The results showed that compared with the color task, the letter task had a longer response time and lower accuracy, which verified the valid manipulation of the attention loads. More importantly, there was no significant difference in averaging performance between the low and high attention loads. By contrast, the individual face processing was impaired under the high attention load relative to the low attentional load. In addition, the advantage of extracting mean emotion over individual emotion was larger under the high attentional load. These results support the power of averaging and provide new evidence that a rather small amount of attention is needed in the ensemble coding of multiple facial expressions.

Long noncoding RNAs (lncRNAs) have attracted significant attention in recent years due to their important roles in many biological processes. Domestic animals constitute a unique resource for understanding the genetic basis of phenotypic variation and are ideal models relevant to diverse areas of biomedical research. With improving sequencing technologies, numerous domestic-animal lncRNAs are now available. Thus, there is an immediate need for a database resource that can assist researchers to store, organize, analyze and visualize domestic-animal lncRNAs. The domestic-animal lncRNA database, named ALDB, is the first comprehensive database with a focus on the domestic-animal lncRNAs. It currently archives 12,103 pig intergenic lncRNAs (lincRNAs), 8,923 chicken lincRNAs and 8,250 cow lincRNAs. In addition to the annotations of lincRNAs, it offers related data that is not available yet in existing lncRNA databases (lncRNAdb and NONCODE), such as genome-wide expression profiles and animal quantitative trait loci (QTLs) of domestic animals. Moreover, a collection of interfaces and applications, such as the Basic Local Alignment Search Tool (BLAST), the Generic Genome Browser (GBrowse) and flexible search functionalities, are available to help users effectively explore, analyze and download data related to domestic-animal lncRNAs. ALDB enables the exploration and comparative analysis of lncRNAs in domestic animals. A user-friendly web interface, integrated information and tools make it valuable to researchers in their studies. ALDB is freely available from http://res.xaut.edu.cn/aldb/index.jsp.

Background In this study, the changes of vaginal microbiome after focused ultrasound (FU) treatment were evaluated to explore the possible mechanism of FU in the treatment of high-risk human papillomavirus (HR-HPV) infection. Methods This study was nested in the FU arm of a prospective cohort study. A total of 37 patients diagnosed with HR-HPV infection-related cervical low-grade squamous intraepithelial lesion (LSIL) who met the inclusion criteria were enrolled in this study from October 2020 to November 2021, and these patients were treated with FU. We used 16S ribosomal RNA (16S rRNA) gene amplicon sequencing to profile the vaginal microbiota composition of patients before and 3 months after FU treatment. Results After FU treatment, HR-HPV was cleared in 24 patients, with a clearance rate of 75.0% (24/32). Lactobacillus iners was the predominant species among all samples. No significant difference was found in alpha-diversity index before and 3 months after FU treatment ( P  > 0.05), but the rarefaction curves showed that the vaginal microbial diversity before FU treatment was higher than that after FU treatment. Linear discriminant analysis (LDA) effect size (LEfSe) showed that Bifidobacterium contributed the most to the difference between the two groups at the genus level, and the abundance after FU treatment was significantly higher than that before treatment ( P  = 0.000). Conclusions The decrease of vaginal microbial diversity may be related to the clearance of HR-HPV infection, and FU treatment contributed to the decrease of vaginal microbial diversity. Increased Bifidobacterium abundance in the vaginal microbiome may be associated with clearance of HR-HPV infection, and FU treatment may contribute to the increase in Bifidobacterium abundance. Trial registration number:  This study was registered in the Chinese Clinical Trial Registry on 23/11/2020 (ChiCTR2000040162).

In plants, the plant-specific RNA polymerase V (Pol V) transcripts non-coding RNAs and provides a docking platform for the association of accessory proteins in the RNA-directed DNA methylation (RdDM) pathway. Various components have been uncovered that are involved in the process of DNA methylation, but it is still not clear how the transcription of Pol V is regulated. Here, we report that the conserved RNA polymerase II (Pol II) elongator, SPT6L, binds to thousands of intergenic regions in a Pol II-independent manner. The intergenic enrichment of SPT6L, interestingly, co-occupies with the largest subunit of Pol V (NRPE1) and mutation of SPT6L leads to the reduction of DNA methylation but not Pol V enrichment. Furthermore, the association of SPT6L at Pol V loci is dependent on the Pol V associated factor, SPT5L, rather than the presence of Pol V, and the interaction between SPT6L and NRPE1 is compromised in spt5l . Finally, Pol V RIP-seq reveals that SPT6L is required to maintain the amount and length of Pol V transcripts. Our findings thus uncover the critical role of a Pol II conserved elongator in Pol V mediated DNA methylation and transcription, and shed light on the mutual regulation between Pol V and II in plants. How to facilitate the transcription of plant-specific RNA Pol V is largely unknown. Liu et al. find that a conserved RNA Pol II elongator, SPT6L, mediates DNA methylation by its association with Pol V and promoting the production of scaffold RNA.

Ultrahot Jupiters (UHJs) possess the most extreme environments among various types of exoplanets, making them ideal laboratories to study the chemical composition and kinetics properties of exoplanet atmosphere with high-resolution spectroscopy. It has the advantage of resolving the tiny Doppler shift and weak signal from exoplanet atmosphere and has helped to detect dozens of heavy elements in UHJs including KELT-9b, WASP-76b, and WASP-121b. MASCARA-4b is a 2.8 days UHJ with an equilibrium temperature of ∼2250 K, which is expected to contain heavy elements detectable with the Very Large Telescope (VLT). In this letter, we present a survey of atoms/ions in the atmosphere of the MASCARA-4b, using the two VLT/ESPRESSO transits data. Cross-correlation analyses are performed on the obtained transmission spectra at each exposure with the template spectra generated by petitRADTRANS for atoms/ions from element Li to U. We confirm the previous detection of Mg, Ca, Cr, and Fe, and report the detection of Rb, Sm, Ti+, and Ba+ with peak signal-to-noise ratios (S/Ns) > 5. We report a tentative detection of Sc+, with peak S/Ns ∼ 6 but deviating from the estimated position. The most interesting discovery is the first-time detection of elements Rb and Sm in an exoplanet. Rb is an alkaline element like Na and K, while Sm is the first lanthanide series element and is by far the heaviest one detected in exoplanets. Detailed modeling and acquiring more data are required to yield abundance ratios of the heavy elements and to understand better the common presence of them in UHJ’s atmospheres.