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.
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).
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).
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.
The high incidence of metastases remains a major hurdle for triple negative breast cancer (TNBC) treatment. Herein, we developed a fairly safe anticancer nanodrug for TNBC treatment by loading ...Epigallocatechin-3-gallate (EGCG) in cross-linked lipoic acid vesicles (EGCG@cLAVs), which cannot only directly kill TNBC cells through inducing apoptosis, but also significantly suppress the TNBC metastasis by metalloproteinases (MMPs) inhibition, a key event in tumor extracellular matrix (ECM) remodeling. The cytotoxicity assay revealed that the ICEGCG 50 of EGCG@cLAVs (85.1 μM) fell in the range of common cytotoxic drugs. The in vitro antimetastasis results disclosed that the EGCG@cLAVs effectively suppressed the migration and invasion of TNBC cells (4T1) with low wound healing rate and relative invasion rate of 19.10 ± 2.12% and 15.0 ± 1.63%, 4.0 and 6.7 times lower than that of control, respectively. The outcomes of animal models revealed that EGCG@cLAVs not only achieved the comparable antitumor effect to that of first-line chemotherapeutic drug DOX, but also reduced the number of lung metastatic nodules from 31.4 (DOX) to 1.4. This nanodrug provides a promising candidate for TNBC therapy.
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.
As an adjuvant drug, alprostadil lipid microsphere injection (Lipo-PGE
) is one of the best-selling drugs in China in recent years. However, the off-label use of Lipo-PGE
is very common. This study ...aimed to investigate the use of Lipo-PGE
and evaluate the clinical effects and economic benefits after administrative intervention on inappropriate use of Lipo-PGE
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
, 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
. 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
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
were also obviously decreased. The administrative intervention obviously reduced the off-label use of Lipo-PGE
. However, there still remains a number of inappropriate uses of Lipo-PGE
. To further improve the rational use of Lipo-PGE
, combination of administrative intervention and real-time clinical pharmacists intervention should be implemented.
Anthracnose, induced by
, poses a substantial economic threat to rubber tree yields and various other tropical crops. Ede1, an endocytic scaffolding protein, plays a crucial role in endocytic site ...initiation and maturation in yeast. Metacaspases, sharing structural similarities with caspase family proteases, are essential for maintaining cell fitness. To enhance our understanding of the growth and virulence of
, we identified a homologue of Ede1 (CgEde1) in
. The knockout of
led to impairments in vegetative growth, conidiation, and pathogenicity. Furthermore, we characterized a weakly interacted partner of CgEde1 and CgMca (orthologue of metacaspase). Notably, both the single mutant Δ
and the double mutant Δ
/Δ
exhibited severe defects in conidiation and germination. Polarity establishment and pathogenicity were also disrupted in these mutants. Moreover, a significantly insoluble protein accumulation was observed in Δ
and Δ
/Δ
strains. These findings elucidate the mechanism by which CgEde1 and CgMca regulates the growth and pathogenicity of
. Their regulation involves influencing conidiation, polarity establishment, and maintaining cell fitness, providing valuable insights into the intricate interplay between CgEde1 and CgMca in
.
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.
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).
Yeast expressing flagellin at cell surface could induce resistance in tomato fruit.
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•Yeast expressing flagellin induce disease resistance against B. cinerea in tomato.•Yeast ...expressing flagellin induce expression of defense-related genes.•Yeast expressing flagellin induce superoxide radical generation.
In this study, bacterial flagellin was expressed at the cell surface of Saccharomyces cerevisiae EBY100 via yeast surface display system. The effect of the yeast on controlling the postharvest decay of tomato fruit caused by Botrytis cinerea and the possible mechanisms were investigated. The results showed that the yeast expressing flagellin at cell surface could significantly induce disease resistance against B. cinerea in tomato wounds. The genes involved in biosynthesis of salicylic acid and jasmonic acid, and plant defense were markedly up-regulated in tomato wounds by the yeast strain expressing flagellin. In addition, application of the yeast strain significantly induced the superoxide radical generation in tobacco leaves and tomato fruit. These findings suggest that expressing flagellin at yeast cell surface may be an effective strategy to increase the biocontrol efficiency of antagonist yeast against disease in postharvest fruit.
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