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Background Proton pump inhibitors (PPIs) remain one of the world’s most frequently prescribed medications and there is a growing number of publications on correct versus incorrect use of PPIs worldwide. The objective of this observational retrospective study was to assess changes in PPI prescribing trends over the past decade and pharmacists’ effect on optimizing PPI prescribing practice at a tertiary hospital in China. Methods We collected the prescriptions of PPIs in our hospital from January 2007 to December 2016. Then the rate of PPI prescribing, the defined daily doses (DDDs) and expenditures were calculated and plotted to show the change in utilization of and expenditure on PPIs. Reasons behind this change and effect of pharmacists’ intervention were evaluated by investigating the rationality of PPI use through sample surveys of patients of pre-intervention (Jul.-Dec. 2015) and post-intervention (Jul.-Dec. 2016). Results In outpatient settings, the rate of PPI prescribing remained almost constant, utilization (from 135,808 DDDs to 722,943 DDDs) and expenditure (from 1.85 million CNY to 7.96 million CNY) increased for the past ten years, dominated by oral formulations and rabeprazole. In contrast, in inpatient settings, the rate of PPI prescribing (from 20.41 to 37.21%), utilization (from 132,329 DDDs to 827,747 DDDs) and expenditure (from 3.15 million CNY to 25.29 million CNY) increased from 2007 to 2015 and then decreased, dominated by injection formulations and omeprazole. Pharmacist interventions could significantly promote the rational use of PPIs (44.00% versus 26.67%), decrease PPI use and reduce patients’ charges ( P  < 0.05). Conclusions The utilization of and expenditure on PPIs grew due to the increase of patients and irrational use of PPI. Pharmacist interventions help to reduce PPI utilization and expenditure and enhance rationality for inpatients, but much work should be done to regulate injection and originator formulas, and improve the rationality in the future.

With the increasing utilization of anticoagulants, the selection of appropriate anticoagulants has emerged as a significant quandary. The objective of this study was to evaluate recent trend in the utilization and expenditure of anticoagulants within a specific region, aiming to provide valuable insights into the optimal choice of anticoagulants across other healthcare facilities. The utilization of anticoagulants was retrospectively analyzed. The data on anticoagulant utilizations in tertiary-care hospitals within a district were collected from January 2019 to December 2023. The expenditure, defined daily doses (DDDs), and defined daily cost (DDC) were calculated. The trends in the utilization and expenditure of anticoagulants were examined using linear regression analysis. From 2019 to 2023, the DDDs of rivaroxaban demonstrated a significant annual increase in most hospitals (p < 0.05). Only a few hospitals exhibited a gradual rise in the consumption of low molecular weight heparin (LMWH) over the same period (p < 0.05). The trend of heparin sodium and warfarin varied across different hospitals. The implementation of the centralized procurement policy, however, resulted in a decline in the consumption of rivaroxaban and LMWH in 2021 and 2022 respectively. The DDC value of rivaroxaban experienced a substantial decrease over the past five years (p = 0.020), declining from 55.20 Chinese Yuan (CNY) in 2019 to 4.28 CNY in 2023. Conversely, there was a slight increase noted in the DDC of heparin sodium during this time frame (p = 0.042). Over the past five years (2019-2023), there has been an increase in the utilization of rivaroxaban and LMWH. However, their expenditure has decreased. In addition, the utilization and expenditure of warfarin and heparin sodium remained relatively stable. The application prospects of rivaroxaban and LMWH are promising.

Melatonin ( -acetyl-5-methoxytryptamine) plays important roles in regulating both biotic and abiotic stress tolerance, biological rhythms, plant growth and development. Sharing the same substrate (tryptophan) for the biosynthesis, melatonin and auxin also have similar effects in plant development. However, the specific function of melatonin in modulating plant root growth and the relationship between melatonin and auxin as well as underlying mechanisms are still unclear. In this study, we found high concentration of melatonin remarkably inhibited root growth in by reducing root meristem size. Further studies showed that melatonin negatively regulated auxin biosynthesis, the expression of PINFORMED (PIN) proteins as well as auxin response in . Moreover, the root growth of the triple mutant was more tolerant than that of wild-type in response to melatonin treatment, suggesting the essential role of PIN1/3/7 in melatonin-mediated root growth. Combination treatment of melatonin and 5-Triiodobenzoic acid (TIBA) did not enhance melatonin-mediated reduction of root meristem size, indicating that polar auxin transport (PAT) may be necessary for the regulation of root meristem size by melatonin treatment. Taken together, this study indicates that melatonin regulates root growth in , through auxin synthesis and polar auxin transport, at least partially.

To evaluate the impact and cost-benefit of clinical pharmacist interventions on inappropriate use of prophylactic acid suppressant in hepatobiliary surgical patients in a Chinese tertiary hospital. A retro-prospective intervention study of patients undergoing elective operations was performed in the Department of Hepatobiliary Surgery of the Affiliated Hospital of Southwest Medical University. Patients admitted from October to December 2015 and from October to December 2016, served as the pre-intervention and the post-intervention group, respectively. Clinical pharmacist interventions in the post-intervention group included real-time monitoring medical records and recommending that surgeons prescribe prophylactic acid suppressants according to the criteria established by the hospital administration. Then, the clinical outcomes of post-intervention group were compared with the pre-intervention group which lacked pharmacist interventions. In addition, cost-benefit analysis was conducted to determine the economic effects of implementing the clinical pharmacist interventions in acid suppressant prophylaxis in perioperative period. Clinical pharmacist interventions significantly decreased the rate of the use of no indications for prophylactic acid suppressant and of the cases of inappropriate drug selection, dose, route, replacement and prolonged duration of prophylaxis (P < 0.05 or P < 0.001), resulting in significant increase by 10.65% in the percentage of cases adhering to all the criteria (P < 0.001). Moreover, significant reductions were found in the average usage quantity (P<0.001), mean cost (P = 0.03) and mean duration (P < 0.001) of prophylaxis acid suppressant. The ratio of the mean cost savings for acid suppressants to the mean cost of pharmacist time was 13.61:1. The clinical pharmacist's real-time interventions facilitated the rational use of prophylactic acid suppressant and resulted in favorable economic outcomes in hepatobiliary surgery.

Key message Overexpression of HbWRKY40 induces ROS burst in tobacco and increases disease resistance in Arabidopsis; RNA-seq and ChIP assays revealed the regulatory network of HbWRKY40 in plant defense. WRKY, a family of plant transcription factors, are involved in the regulation of numerous biological processes. In rubber tree Hevea brasiliensis , the roles of WRKYs remain poorly understood. In the present study, a total of 111 genes encoding putative HbWRKY proteins were identified in the H. brasiliensis genome. Among these genes, HbWRKY40 transcripts were significantly induced by Colletotrichum gloeosporioides and salicylic acid. To assess its roles in plant defense, HbWRKY40 was over-expressed in Nicotiana benthamiana and Arabidopsis thaliana . The results showed that HbWRKY40 significantly induced reactive oxygen species burst in N. benthamiana and increased resistance of Arabidopsis against Botrytis cinerea . Transient expression in mesophyll cell protoplasts of H. brasiliensis showed that HbWRKY40 localizes at nuclei. In addition, transcripts of 145 genes were significantly up-regulated and 6 genes were down-regulated in the protoplasts over-expressing HbWRKY40 based on the RNA-seq analysis. Among these potential downstream targets, 12 genes contain potential WRKY-binding sites at the promoter regions. Further analysis through chromatin immunoprecipitation revealed that 10 of these 12 genes were the downstream targets of HbWRKY40. Taken together, our findings indicate that HbWRKY40 plays an important role in the disease resistance by regulating defense-associated genes in H. brasiliensis.

Background Mitochondrial fusion is vital for cellular function and has been increasingly linked to cancer development. Kidney renal papillary cell carcinoma (KIRP), the second most common renal cell carcinoma, presents diverse prognostic outcomes. Identifying novel biomarkers is critical for improving prognosis and treatment response in KIRP. Objective This study aims to explore the gene expression associated with mitochondrial fusion and establish a novel gene signature model to predict KIRP prognosis and cisplatin sensitivity. Methods We analyzed RNA sequencing data and clinical records of 285 KIRP patients from The Cancer Genome Atlas (TCGA). LASSO regression identified four key mitochondrial fusion-related genes (BNIP3, GDAP1, MIEF2, PRKN). Multivariate Cox regression evaluated their association with overall survival. Risk stratification was developed based on gene expression. We assessed immunotherapy responses using checkpoint inhibitor scores, tumor mutation burden, TIDE scores, and tumor microenvironment characteristics. Cisplatin sensitivity was evaluated via correlation analysis of gene expression levels and half-maximal inhibitory concentration (IC50). In vitro loss- and gain-of-function experiments in KIRP cell lines (Caki-2, ACHN) assessed MIEF2's role in cisplatin sensitivity. Results The gene signature successfully stratified patients into high- and low-risk groups, with significant survival differences. The area under the ROC curve (AUC) for the risk model was 0.782. MIEF2 was notably associated with cisplatin sensitivity, confirmed through functional experiments. Patients in the high-risk group exhibited lower MIEF2 expression and increased cisplatin sensitivity.

Arabidopsis thaliana BOTRYTIS-INDUCED KINASE1 (BIK1) regulates immune responses to a distinct class of pathogens. Here, mechanisms underlying BIK1 function and its interactions with other immune response regulators were determined. We describe BIK1 function as a component of ethylene (ET) signaling and PAMP-triggered immunity (PTI) to fungal pathogens. BIK1 in vivo kinase activity increases in response to flagellin peptide (fig22) and the ET precursor 1-aminocyclopropane-1-carboxylic acid (ACC) but is blocked by inhibition of ET perception. BIK1 induction by flg22, ACC, and pathogens is strictly dependent on EIN3, and the bik1 mutation results in altered expression of ET-regulated genes. BIK1 site-directed mutants were used to determine residues essential for phosphorylation and biological functions in planta, including PTI, ET signaling, and plant growth. Genetic analysis revealed flg22-induced PTI to Botrytis cinerea requires BIK1, EIN2, and HUB1 but not genes involved in salicylate (SA) functions. BIK1-mediated PTI to Pseudomonas syringae is modulated by SA, ET, and jasmonate signaling. The coil mutation suppressed several bik1 phenotypes, suggesting that may act as a repressor of BIK1 function. Thus, common and distinct mechanisms underlying BIK1 function in mediating responses to distinct pathogens are uncovered. In sum, the critical role of BIK1 in plant immune responses hinges upon phosphorylation, its function in ET signaling, and complex interactions with other immune response regulators.

As an adjuvant drug, alprostadil lipid microsphere injection (Lipo-PGE 1 ) is one of the best-selling drugs in China in recent years. However, the off-label use of Lipo-PGE 1 is very common. This study aimed to investigate the use of Lipo-PGE 1 and evaluate the clinical effects and economic benefits after administrative intervention on inappropriate use of Lipo-PGE 1 in neurosurgical patients in a Chinese tertiary hospital. Administrative interventions were implemented from January to December 2018 by reducing the procurement volume of Lipo-PGE 1 , judging the rationality of medical records, and establishing reward and punishment mechanisms. Administrative interventions significantly decreased prescription rate (49.98% vs 22.49%), utilization (22,311 DDDs vs 8334 DDDs), drug use density (43.52 DDDs/TID vs 15.84 DDDs/TID), total expenditure (3.58 million RMB vs 1.30 million RMB ), and average expenditure (2025.04 RMB vs 1466.49 RMB ) of Lipo-PGE 1 . To our delight, these intervention effects were maintained or even better in the 1-year post-intervention period. Moreover, in the intervention and post-intervention phases, the Lipo-PGE 1 use for no indications as well as inappropriate drug dose, frequency, menstruum type, combination, and contraindication were markedly reduced. Besides, the mean costs ( P  < 0.001), and mean duration ( P  < 0.001) of Lipo-PGE 1 were also obviously decreased. The administrative intervention obviously reduced the off-label use of Lipo-PGE 1 . However, there still remains a number of inappropriate uses of Lipo-PGE 1 . To further improve the rational use of Lipo-PGE 1 , combination of administrative intervention and real-time clinical pharmacists intervention should be implemented.

We studied the function of Arabidopsis (Arabidopsis thaliana) Botrytis Susceptible1 Interactor (BOI) in plant responses to pathogen infection and abiotic stress. BOI physically interacts with and ubiquitinates Arabidopsis BOS1, an R2R3MYB transcription factor previously implicated in stress and pathogen responses. In transgenic plants expressing the BOS1-β-glucuronidase transgene, β-glucuronidase activity could be detected only after inhibition of the proteosome, suggesting that BOS1 is a target of ubiquitin-mediated degradation by the proteosome. Plants with reduced BOI transcript levels generated through RNA interference (BOI RNAi) were more susceptible to the necrotrophic fungus Botrytis cinerea and less tolerant to salt stress. In addition, BOI RNAi plants exhibited increased cell death induced by the phytotoxin α-picolinic acid and by a virulent strain of the bacterial pathogen Pseudomonas syringae, coincident with peak disease symptoms. However, the hypersensitive cell death associated with different race-specific resistance genes was unaffected by changes in the level of BOI transcript. BOI expression was enhanced by B. cinerea and salt stress but repressed by the plant hormone gibberellin, indicating a complex regulation of BOI gene expression. Interestingly, BOI RNAi plants exhibit reduced growth responsiveness to gibberellin. We also present data revealing the function of three Arabidopsis BOI-RELATED GENES (BRGs), which contribute to B. cinerea resistance and the suppression of disease-associated cell death. In sum, BOI and BRGs represent a subclass of RING E3 ligases that contribute to plant disease resistance and abiotic stress tolerance through the suppression of pathogen-induced as well as stress-induced cell death.

ObjectiveThe objective of this study was to describe the trend in prescribing proton pump inhibitor (PPI) use and expenditure in both secondary and tertiary hospitals in China between 2017 and 2021.DesignMulticentre cross-sectional survey.SettingChina, 14 medical centres, January 2017 to December 2021.Participants537 284 participants who were treated with PPI in 14 medical centres of China, between January 2017 and December 2021 were included.Main outcomes and measuresThe rate of PPI prescriptions, the defined daily doses (DDDs), DDDs/1000 inhabitants per day (DDDs/TID) and expenditure were analysed and plotted to demonstrate changes in prescription PPI use and expenditure.ResultsFor both outpatient and inpatient settings, the rate of PPI prescribing decreased from 2017 to 2021. In outpatient settings, decreased slightly from 3.4% to 2.8%, however, in inpatient settings, showed a progressive decrease from 26.7% to 14.0%. The overall rate of injectable PPI prescriptions for inpatients decreased significantly from 21.2% to 7.3% between 2017 and 2021. Decreased trends in usage of oral PPI were observed (from 280 750 DDDs to 255 121 DDDs) between 2017 and 2021. However, usage of injectable PPI showed a significantly decrease from 191 451 DDDs to 68 806 DDDs from 2017 to 2021. In terms of DDDs/TID of PPI for inpatients decreased dramatically from 52.3 to 30.2 for the past 5 years. Expenditure on oral PPI decreased slightly from ¥1.98 million (Chinese currency Renminbi ‘yuan’) to ¥1.23 million for the past 5 years, whereas expenditure on injectable PPI showed a marked decrease from ¥2.61 million to ¥0.94 million. There was no statistical difference in both PPI use and expenditure between secondary and tertiary hospitals during the study period.ConclusionsDecreased PPI use and expenditure were observed among secondary and tertiary hospitals over the past 5 years (2017–2021).