Betulin ameliorates neuronal apoptosis and oxidative injury via DJ-1/Akt/Nrf2 signaling pathway after subarachnoid hemorrhage.

AIMS: We aimed to resolve the uncertainty as to whether betulin exerted neuroprotection on early brain injury (EBI) caused by subarachnoid hemorrhage (SAH), and to investigate the related molecular mechanisms. METHODS: Bioinformatic analysis was performed to pre-study the differently expressed genes (DEGs) and the possible signaling pathways. Rat and cellular model of SAH were introduced in this study, and betulin, an activator of DJ-1 protein, was administered to reveal the effect. Gross assessment regarding mortality, neurofunctions, SAH grade, brain water content (BWC) along with multiple cellular and molecular studies in vivo or/and in vitro such as immunofluorescence (IF) staining, western blot (WB), reactive oxygen species (ROS) assay, and flow cytometry (FCM) were all conducted after SAH induction to verify the protective effect and the relevant mechanisms of DJ-1 in diverse levels. In addition, MK2206 (selective inhibitor of Akt) and iRNADj-1 (interfering RNA to Dj-1) were utilized to confirm the mechanisms of the effect. RESULTS: The data from our study showed that DJ-1 protein was moderately expressed in neurons, microglia, and astrocytes; its level in brain tissue elevated and peaked at 24-72 h after SAH induction. Betulin could efficaciously induce the expression of DJ-1 which in turn activated Akt and Bcl-2, and anti-oxidative enzymes SOD2 and HO-1, functioning to reduce the activation of cleaved caspase-3 (c-Casp-3) and reactive oxygen species (ROS). The induced DJ-1 could upregulate the expression of Nrf2. However, Akt seemed no direct effect on elevating the expression of Nrf2. DJ-1 alone could as well activate Akt-independent antiapoptotic pathway via suppressing the activation of caspase-8 (Casp-8). CONCLUSIONS: Betulin which was a potent agonist of DJ-1 had the ability to induce its expression in brain tissue. DJ-1 had neuroprotective effect on EBI through comprehensive mechanisms, including facilitating intrinsic and extrinsic antiapoptotic pathway, and reducing oxidative injury by upregulating the expression of redox proteins. Betulin as an inexpensive drug showed the potential for SAH treatment.

Research progress and challenges of stem cell therapy for ischemic stroke.

Ischemic stroke is a significant global cause of death and disability. Currently, treatment options for acute ischemic stroke are limited to intravenous thrombolysis and mechanical recanalization. Therefore, novel neuroprotective strategies are imperative. Stem cell transplantation possesses the capabilities of differentiation, proliferation, neuronal replacement, nerve pathway reconstruction, secretion of nerve growth factors, and enhancement of the microenvironment; thus, it is a potential therapeutic approach for ischemic stroke. In addition, the immunomodulatory function of stem cells and the combined treatment of stem cells and exosomes exhibit a favorable protective effect on brain injury and neurological dysfunction following stroke. Meanwhile, the theory of microbiota-gut-brain axis provides us with a novel perspective for comprehending and managing neurological diseases. Lastly, stem cell transplantation has demonstrated promising outcomes not only in treating ischemic stroke but also in dealing with other neurological disorders, such as brain tumors. Furthermore, challenges related to the tissue source, delivery method, immune response, and timing of transplantation still need to be addressed to optimize the treatment.

Cleavage of gasdermin by apoptotic caspases triggers pyroptosis restricting bacterial colonization in Hydra.

Gasdermin (GSDM) proteins, as the direct executors of pyroptosis, are structurally and functionally conserved among vertebrates and play crucial roles in host defense against infection, inflammation, and cancer. However, the origin of functional GSDMs remains elusive in the animal kingdom. Here, we found that functional GSDME homologs first appeared in the cnidarian. Moreover, these animal GSDME homologs share evolutionarily conserved apoptotic caspase cleavage sites. Thus, we verified the functional conservation of apoptotic caspase-GSDME cascade in Hydra, a representative species of cnidarian. Unlike vertebrate GSDME homologs, HyGSDME could be cleaved by four Hydra caspase homologs with caspase-3 activity at two sites. Furthermore, in vivo activation of Hydra caspases resulted in HyGSDME cleavage to induce pyroptosis, exacerbating injury and restricting bacterial burden, which protects Hydra from pathogen invasion. In conclusion, these results suggest that GSDME-dependent pyroptosis may be an ancient and conserved host defense mechanism, which may contribute to better understanding on the origin and evolution of GSDMs.

Population Pharmacokinetics of Isavuconazole in Adult: A Systematic Review.

Isavuconazole (ISA) is a second generation broad-spectrum triazole antifungal drug derived from voriconazole structure, and its oral capsules is currently the only oral preparation approved for invasive mucormycosis. In recent years, population pharmacokinetic studies of ISA have been reported continuously. This paper aims to summarize the characteristics of population pharmacokinetic models of ISA in adults, and provide theoretical basis for individualized administration of ISA. We systematically searched PubMed, Embase, CNKI, Wanfang, VIP and other databases to collect population pharmacokinetic models published from the establishment of the database to March 2023. A total of 6 studies were included in this review, including healthy men and women, invasive fungal infections with malignant tumors or neutropenia, solid organ transplantation. The dose of ISA was 40-400mg for single-dose. The multiple-dose of ISA was 200mg every 8 hours for the first 48 hours and then 200mg once daily. All studies used a two-compartment model, first-order elimination. For oral formulations, except for one study that used first-order absorption, the others used Weibull absorption. Body mass index (BMI) was the most common covariable, followed by total body weight, lean body mass, race, sex, population type (healthy volunteers/patients), and creatinine clearance. These studies included several covariates, and the clearance rate (CL) was similar among populations. In the future, external validation and population pharmacokinetic studies in special populations such as patients with severe liver disease and ECMO support are needed.

GPNMB Ameliorates Neuroinflammation Via the Modulation of AMPK/NFκB Signaling Pathway After SAH in Mice.

Glycoprotein non-metastatic melanoma protein B (GPNMB) got its name from the first discovery in a cell line of non-metastatic melanoma. Later studies found that GPNMB is widely expressed in various tissues and cells of the human body, most abundant in neural tissue, epithelial tissue, bone tissue, and monocyte-macrophage system. GPNMB has been shown to have anti-inflammatory effects in a variety of neurological diseases, however, it has not been reported in subarachnoid hemorrhage (SAH). Male CD-1 mice were used and intra-arterial puncture method was applied to establish the SAH model. Exogenous recombinant GPNMB (rGPNMB) was injected intracerebroventricularly 1 h after SAH. SAH grading, brain edema and blood-brain barrier (BBB) integrity were quantified, and neurobehavioral tests were performed to evaluate the effect of GPNMB on the outcome. Dorsomorphin, the selective inhibitor on AMPK was introduced to study the downstream signaling through which the GPNMB works. Furthermore, western blot, immunofluorescence staining and ELISA were utilized to confirm the signaling. After SAH, GPNMB expression increased significantly as a result of the inflammatory response. GPNMB was expressed extensively in mouse microglia, astrocytes and neurons. The administration of rGPNMB could alleviate brain edema, restore BBB integrity and improve the neurological outcome of mice with SAH. GPNMB treatment significantly magnified the expression of p-AMPK while p-NFκB, IL-1ß, IL-6 and TNF-α were suppressed; in the meantime, the combined administration of GPNMB and AMPK inhibitor could decrease the intensity of p-AMPK and reverse the quantity of p-NFκB and the above inflammatory cytokines. GPNMB has the potential of ameliorating the brain edema and neuroinflammation, protecting the BBB and improving the neurological outcome, possibly via the AMPK/NFκB signaling pathway.

The Influence of Diagnosis Intervention Packet Policy Intervention on Medication Structure and Drug Cost of Elderly Hypertensive Inpatients in China: A Multicenter Interrupted Time-Series Analysis.

Background: DIP is a new medical insurance payment system developed in China which was implemented in Guangzhou in January 2018, but few studies have focused on its intervention effect on the drug burden of elderly hypertensive patients. Methods: Nine medical institutions in Guangzhou, China, were selected, among which, daily full medical orders of elderly hypertensive inpatients from 2016 to 2020 were randomly collected. To assess the impact of DIP policy intervention on patient drug burden, we took the data after policy implementation in January 2018, as the intervention data, and applied a segmented regression model with interrupted time series to analyze the trend and changes in average daily drug costs per month and medication structure, stratified by age, sex, and inpatient department. Results: A total of 34,276 elderly hypertensive patients' daily full medical orders were obtained. The immediate level change of drug costs after intervention was -23.884 RMB/month (P = 0.652), and the trend change was statistically significant (-15.642 RMB/month, P = 0.002). The relative cumulative effect at the end of the study was -78.860% (95% CI: -86.087% to -69.076%), and the intervention effect was more significant in surgical and male patients. The analysis of drug structure changes showed that after the implementation of the DIP policy intervention, the proportion of anti-infective drugs, anti-tumor drugs, and biological products all showed a significant downward trend (P < 0.05), while nutritional drugs showed a significant upward trend (P = 0.011), but no immediate horizontal change in slope was observed. Conclusion: The typical practice in China showed that DIP policy intervention can improve the drug burden of elderly hypertensive hospitalized patients and has a stable long-term effect, and the intervention effect is not consistent across different clinical department and populations with different characteristics, and it would also cause changes in the medication structure.

Quantification of Venetoclax for Therapeutic Drug Monitoring in Chinese Acute Myeloid Leukemia Patients by a Validated UPLC-MS/MS Method.

Venetoclax has emerged as a breakthrough for treatment of leukemia with a wide interindividual variability in pharmacokinetics. Herein, a rapid, sensitive, and reliable UPLC-MS/MS method for quantification of venetoclax in plasma was developed and validated. The method was operated in the multiple-reaction monitoring (MRM) mode to detect venetoclax at m/z transition 868.5 > 321.0 and IS at 875.5 > 321.0, respectively. Protein precipitation prior to injection into the LC-MS/MS and the analyte was separated on an ACQUITY UPLC BEH C18 column by gradient elution with acetonitrile and 0.1% formic acid in water. Linear calibration curves were obtained in the range of 25−8000 ng/mL. The specificity, recovery, matrix effect, and stability also met the acceptance criteria of FDA guidance. The method was successfully applied to analyze plasma in acute myeloid leukemia (AML) patients. The peak plasma concentration (Cmax) of venetoclax in Chinese AML patient was 2966.0 ± 1595.0 ng/mL while the trough concentration (Cmin) was 1018.0 ± 729.4 ng/mL. Additionally, Cmax and Cmin showed a positive correlation with AST levels. Furthermore, Cmax was significantly higher in the older patients. The present method can be applied for TDM of venetoclax in treatment of hematological cancers.

Recent advances in ferroptosis and therapeutic strategies for glioblastoma.

Ferroptosis is an emerging form of cell death characterized by the over-accumulation of iron-dependent lipid peroxidation. Ferroptosis directly or indirectly disturbs glutathione peroxidases cycle through diverse pathways, impacting the cellular antioxidant capacities, aggravating accumulation of reactive oxygen species in lipid, and it finally causes oxidative overload and cell death. Ferroptosis plays a significant role in the pathophysiological processes of many diseases. Glioblastoma is one of the most common primary malignant brain tumors in the central nervous system in adults. Although there are many treatment plans for it, such as surgical resection, radiotherapy, and chemotherapy, they are currently ineffective and the recurrent rate is almost up to 100%. The therapies abovementioned have a strong relationship with ferroptosis at the cellular and molecular level according to the results reported by numerous researchers. The regulation of ferroptosis can significantly determine the outcome of the cells of glioblastoma. Thus ferroptosis, as a regulated form of programed cell death, has the possibility for treating glioblastoma.

Incidence of venous thromboembolism and hemorrhage in Chinese patients after pulmonary lobectomy: mechanical prophylaxis or mechanical prophylaxis combined with pharmacological prophylaxis: a randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) and postoperative bleeding are important complications of lung resection surgery. We investigated the preventive effect of mechanical prophylaxis versus pharmacological prophylaxis after lobectomy, and evaluated the effect of both on the incidence of hemorrhagic events. METHODS: A prospective study of 424 lobectomies with moderate to high risk of VTE (Caprini risk score <5) in a single center was performed from April 2020 to March 2021. Patients were 1:1 randomly allocated to mechanical prophylaxis or to the low-molecular-weight heparin (LMWH)-combination-prophylaxis. The incidence of postoperative thrombotic and bleeding events and relevant factors of the two groups were analyzed. RESULTS: A total of 410 participants, with 202 and 208 in the mechanical prophylaxis and LMWH-combination-prophylaxis groups respectively, were selected for analysis. Both groups had similar baseline and clinical characteristics. There were no cases of VTE or major bleeding during the study, but the incidence rate of minor bleeding in the LMWH-combination-prophylaxis group was significantly higher than mechanical prophylaxis group [odds ratio (OR) 0.035, 95% confidence interval (CI): 0.011-0.113]. CONCLUSIONS: A case-by-case risk assessment of VTE and hemorrhage remains necessary to determine the most appropriate method of thrombosis prophylaxis for patients undergoing pulmonary surgery. Mechanical prophylaxis may be preferable for lung cancer patients with moderate to high risk of VTE (Caprini risk score <5) undergoing lobectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100051073.

Oral delivery of infliximab using nano-in-microparticles for the treatment of inflammatory bowel disease.

The anti-tumor necrosis factor-α (anti-TNF-α) blocker, has shown great efficacy for the treatment of inflammatory bowel disease (IBD). However, systemic exposure to it can cause considerable safety problems due to reduced suppression of the systemic immune response and loss of response to the production of anti-drug antibodies. Thus, we try to devise a targeted vehicle system for oral administration of anti-TNF-α antibodies for the treatment of IBD. In the present study, we developed an oral Infliximab (IFX) loaded nano-in-microparticles, based on chitosan (CS)/carboxymethyl chitosan (CMC) and alginate (Alg), which could protect IFX from the harsh environment of the gastrointestinal tract and produce targeted drug delivery to the inflamed intestine. In vivo studies demonstrated that the IFX loaded nano-in-micro vehicle can alleviate colitis by ameliorating inflammation and maintaining the intestinal epithelial barrier.

Elevation of Serum Cytokine Profiles and Liver Metabolomic Normalization in Early Convalescence of COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) has become a global public health concern. We aimed to study the cytokine profile during the convalescent phase and its association with liver functions. We performed a retrospective study to investigate the longitudinal dynamic serum cytokine, liver function, and metabolomic profiles, as well as their potential correlations, from the viral replication phase to early convalescence. Our results demonstrated that liver injury was common. Liver injury was significantly associated with higher levels of interleukin (IL)-6 and IL-10 (p < 0.05). However, alanine aminotransferase levels decreased during the first week after hospital discharge (p < 0.01). In parallel, T-cell and B-cell immune response-stimulating cytokine IL-4, but not IL-2, was significantly elevated (p < 0.05). Furthermore, interferon-γ (IFN-γ) and tumor necrosis factor-α (TFN-α) levels increased, in contrast to the decrease in IL-6 and IL-10 levels; liver function returned to normal. The metabolomic analysis supported active recovery during early convalescence of COVID-19 patients that had distinct metabolic profiles associated with the hepatic tricarboxylic acid cycle, amino acid metabolism, and lipid metabolism. In addition, we identified a metabolomic association of IL-4 with liver repair. Our findings suggest that discharged patients continue to recover from the physiological effects of COVID-19, and the association of IL-4, IL-6, and IL-10 levels with metabolic changes and liver function repair may have important implications for clinical manifestations and treatment of COVID-19.

Ferroptosis and Its Multifaceted Roles in Cerebral Stroke.

Ferroptosis is a unique regulated cell death defined by the intracellular iron overload and distinct biological features compared with other well-known programmed cell death. Ferroptosis can be triggered by many causes including decreased expression of glutathione (GSH), inhibition of the function of glutathione-dependent peroxidase 4 (GPX4), and system xc -, all of which finally lead to the over-accumulation of lipid peroxides in the cell. Ferroptosis has been reported to play an important role in the pathophysiological process of various cancers. In recent years, much evidence also proved that ferroptosis is involved in the progress of cerebral stroke. In this review, we summarized the characteristics of ferroptosis and the potential relationship between ferroptosis and ischemic and hemorrhagic stroke, to provide new targets and ideas for the therapy of stroke.

Tailor-Made Nanomaterials for Diagnosis and Therapy of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide due to its aggressiveness and the challenge to early diagnosis and treatment. In recent decades, nanomaterials have received increasing attention for diagnosis and therapy of PDAC. However, these designs are mainly focused on the macroscopic tumor therapeutic effect, while the crucial nano-bio interactions in the heterogeneous microenvironment of PDAC remain poorly understood. As a result, the majority of potent nanomedicines show limited performance in ameliorating PDAC in clinical translation. Therefore, exploiting the unique nature of the PDAC by detecting potential biomarkers together with a deep understanding of nano-bio interactions that occur in the tumor microenvironment is pivotal to the design of PDAC-tailored effective nanomedicine. This review will introduce tailor-made nanomaterials-enabled laboratory tests and advanced noninvasive imaging technologies for early and accurate diagnosis of PDAC. Moreover, the fabrication of a myriad of tailor-made nanomaterials for various PDAC therapeutic modalities will be reviewed. Furthermore, much preferred theranostic multifunctional nanomaterials for imaging-guided therapies of PDAC will be elaborated. Lastly, the prospects of these nanomaterials in terms of clinical translation and potential breakthroughs will be briefly discussed.

Cost-effectiveness of rivaroxaban versus warfarin in non-valvular atrial fibrillation patients with chronic kidney disease in China.

WHAT IS KNOWN AND OBJECTIVE: In non-valvular atrial fibrillation (NVAF) patients with chronic kidney disease (CKD), rivaroxaban was not inferior to warfarin in preventing stroke and systemic embolism. However, a comparative evaluation of the cost-effectiveness of rivaroxaban and warfarin therapies for NVAF patients at different renal function levels has not yet been reported, and this study aimed to estimate the cost-effectiveness of rivaroxaban compared with warfarin in Chinese NVAF patients with CKD. METHODS: A Markov model was constructed to estimate quality-adjusted life years (QALYs) and lifetime costs associated with the use of rivaroxaban relative to warfarin in patients with NVAF at different estimated glomerular filtration rate (eGFR) levels as follows: 30 to <50, 50 to <80 and ≥80 mL/min. Input parameters were sourced from the clinical literature. Probabilistic sensitivity analyses were performed to assess model uncertainty. RESULTS AND DISCUSSION: The incrementalQALYs with rivaroxaban was slightly increased by approximately 0.3 QALY as compared with that with warfarin in all the subgroups, resulting in an ICER of $9,736/QALY (eGFR, 30 to <50 mL/min), $9,758/QALY (50 to <80 mL/min) and $9,969/QALY (≥80 mL/min). The probabilistic sensitivity analysis suggested a chance of >80% that the ICER would be lower than the willingness-to-pay threshold of three times the GDP of China in 2019 in all the subgroups. Results were consistent even under the assumption of anticoagulant discontinuation after major bleeding events. The model was most sensitive to event-free-related utility and survival rates. WHAT IS NEW AND CONCLUSION: The existing evidence supports the cost-effectiveness of rivaroxaban therapy as an alternative anticoagulant to warfarin for patients with NVAF at different renal function levels.

Progress in Stem Cell Therapy for Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) is one of the serious neurological diseases that occur in young people with high morbidity and disability. However, there is still a lack of effective treatments for it. Stem cell (SC) treatment of SCI has gradually become a new research hotspot over the past decades. This article is aimed at reviewing the research progress of SC therapy for SCI. METHODS: Review the literature and summarize the effects, strategies, related mechanisms, safety, and clinical application of different SC types and new approaches in combination with SC in SCI treatment. RESULTS: A large number of studies have focused on SC therapy for SCI, most of which showed good effects. The common SC types for SCI treatment include mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs). The modes of treatment include in vivo and in vitro induction. The pathways of transplantation consist of intravenous, transarterial, nasal, intraperitoneal, intrathecal, and intramedullary injections. Most of the SC treatments for SCI use a number of cells ranging from tens of thousands to millions. Early or late SC administration, application of immunosuppressant or not are still controversies. Potential mechanisms of SC therapy include tissue repair and replacement, neurotrophy, and regeneration and promotion of angiogenesis, antiapoptosis, and anti-inflammatory. Common safety issues include thrombosis and embolism, tumorigenicity and instability, infection, high fever, and even death. Recently, some new approaches, such as the pharmacological activation of endogenous SCs, biomaterials, 3D print, and optogenetics, have been also developed, which greatly improved the application of SC therapy for SCI. CONCLUSION: Most studies support the effects of SC therapy on SCI, while a few studies do not. The cell types, mechanisms, and strategies of SC therapy for SCI are very different among studies. In addition, the safety cannot be ignored, and more clinical trials are required. The application of new technology will promote SC therapy of SCI.

SPOCK1: a multi-domain proteoglycan at the crossroads of extracellular matrix remodeling and cancer development.

The SPARC/osteonectin, CWCV and Kazal-like domains proteoglycan 1 (SPOCK1) is a highly conserved, multi-domain proteoglycan that regulates the dynamic equilibrium of extracellular matrix (ECM). Besides, SPOCK1 is one of the key regulatory genes in the tumor ECM dynamic homeostasis process, which activates many molecular signaling pathways (such as EMT process, Wnt/ß-catenin, PI3K/Akt, and mTOR/S6K signaling pathways). This activation leads to ECM remodeling and promotes cell proliferation and invasion, but inhibits cell apoptosis. Whereas there is immense information about SPOCK1's roles in different biological settings, there is need for further studies that interrogate this protein as a potential therapeutic target in cancer.

Severe cerebral edema induced by watershed shift after bypass in a patient with chronic steno-occlusive disease: a case report and short literature review.

BACKGROUND: Carotid occlusive disease is a type of progressive disease resulting in ischemic stroke. Extracranial-intracranial bypass surgery represents a valid therapeutic option when medical treatment does not make effects. The appearance of cerebral edema following bypass is common during acute stage. Additionally, there are many causes of mild cerebral edema, such as hemodynamic changes, venous congestion and others. However, severe edema involving large brain tissue, which presents as reversible aphasia and hemiplegia, remains to be elucidated. CASE PRESENTATION: A 55-year-old man was admitted to the neurosurgery department for repeated dizziness for over a year and sudden onset of syncope 1 month prior, and he was diagnosed with carotid occlusive disease. After surgical contraindications were excluded, dual bypass and encephalo-duro-myo-synangiosis were performed. Although blood pressure and fluid management were strictly under control promptly after surgery, massive cerebral edema involving the left anterior cerebral artery and middle cerebral artery territories occurred from the 6th day after surgery. Additionally, no discernible cerebral infarction or hemorrhage occurred. Moreover, the cerebral blood flow of the middle cerebral artery displayed an early decrease followed by delayed elevation on the left side. Without restricting the spreading of cerebral edema, life-threatening cerebral herniation could develop at any time. Mannitol and furosemide were administered for impending cerebral herniation. The amelioration of symptoms was noticed on the 16th day after surgery. The patient felt relief on the 21st day after surgery. Digital subtraction angiography performed on the 180th day after surgery demonstrated the patency of dual anastomosed vessels, and the patient recovered without any permanent neurological deficit. CONCLUSION: Based on changes in cerebral blood flow and reversible symptoms, the "watershed shift" phenomenon could explain such a severe deficit. However, this deficit was not the same as the classical presentation of the "watershed shift", which involves a moderate amount of brain tissue and presents significant increases in cerebral blood flow. In addition to the "watershed shift", a swollen temporal muscle may also participate in the progression of focal edema.

[Management of a colon cancer patient complicated with COVID-19].

OBJECTIVE: To explore the feasibility of radical resection for cancer patients complicated with coronavirus disease 2019 (COVID-19). METHODS: The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed. RESULTS: The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice. CONCLUSIONS: The case indicates that radical resection can be performed in SARS-CoV-2 patients with twice-negative SARS-CoV-2 nucleic acid testing results.

Pharmacist-driven multidisciplinary initiative continuously improves postoperative nausea and vomiting in female patients undergoing abdominal surgery.

WHAT IS KNOWN AND OBJECTIVE: The incorrect or insufficient prophylaxis of postoperative nausea and vomiting (PONV) is common in practice. A clinical pharmacist-led guidance team (CPGT) was established and included in general surgery teams. OBJECTIVE: This study aimed to evaluate the effects of the CPGT on the improvement of PONV and prophylaxis administration. METHODS: A prospective before-after study was conducted on 156 female patients undergoing abdominal surgery at a Chinese tertiary teaching hospital from December 2016 to December 2017. A total of 82 patients were enrolled in the preintervention period, and 74 patients were included in the post-intervention period. The CPGT established the evidence-based criteria for prophylactic anti-emetic administration and conducted interventions, including a review of medical records, provision of feedback, educational outreach, and dedicated support. Primary outcomes included the incidence of PONV within 24 hours of surgery, administered number of prophylactic anti-emetics, and accuracy of the timing for prophylactic anti-emetics. Outcomes were analysed by logistic regression or multivariable linear regression. RESULTS AND DISCUSSION: After intervention, patients reported significantly less PONV (33.78% vs 56.10%; odds ratio [OR]: 0.29; numbers needed to treat [NNT]: 3.47), vomiting (29.73% vs 45.12%; OR: 0.42; NNT: 5.16) and nausea (31.08% vs 56.10%; OR: 0.24; NNT: 3.19) within 24 hours of surgery. The accuracy of the timing for prophylactic anti-emetics significantly increased (OR: 3.66; P: .003). Anaesthesiologists administered increased numbers of prophylactic anti-emetics (OR: 5.82; P < .001). The improvement of PONV did not decrease during the four-month period after intervention (P: .639). WHAT IS NEW AND CONCLUSION: The CPGT is a valuable service model to continuously improve PONV and optimize prophylaxis administration.

Determination and pharmacokinetic study of skimmin by UHPLC-MS/MS in rat plasma.

Skimmin, a major active ingredient derived from Hydrangea paniculata, has been considered to possess various pharmacological activities, including renoprotective activity, anti-inflammatory, anti-cancer, and antiamoebic properties. However, no investigation has reported the quantification and pharmacokinetics of skimmin in biomatrices. In the present study, we established and validated an ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the estimation of skimmin in rat plasma, which was successfully applied to explore the oral and intravenous pharmacokinetics of skimmin. All plasma samples were obtained following blood collection from the rat' tail vein and prepared using the protein precipitation method with acetonitrile. Separation of the analyte and internal standard (IS) magnoflorine was achieved by a reversed phase T3 column. The mobile phase consisted of water containing 0.1 % formic acid and acetonitrile with a gradient elution program. The analytical run time was 4 min with a flow rate of 0.3 mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI).Multiple reaction monitoring transitions were performed at m/z of 325.34 → 163.00 and 342.24 → 57.98 for skimmin and IS, respectively. The method demonstrated good linearity in the range of 2-2000 ng/mL and was validated by US FDA bioanalytical guidelines. A pharmacokinetic study of skimmin was then successfully conducted using the validated method. Hence, the absolute bioavailability of skimmin was approximately 25.08 % with rapid absorption and elimination. This study will be beneficial in better understanding the pharmacological properties and the further development of skimmin.